Plasma butyrylcholinesterase (BChE) is the chief metabolizing enzyme for cocaine in humans. Studies with other substrates indicate that this enzyme is under genetic control and shows population variability, but there are no human studies of its effects on cocaine metabolism or cocaine abuse. This study, in collaboration with Dr. Raymond Woosley, Georgetown University, measures plasma BCHE activity in cocaine users to determine the influence of subject characteristics on enzyme activity and of enzyme activity on cocaine pharmacokinetics and response to cocaine. In addition, cytochrome P450-IID6 genotype is measured, since this enzyme is presumed to be involved in oxidative metabolism of cocaine. Preliminary data from the first 27 cocaine-dependent subjects studied showed that all had plasma BCHE activity within the published "normal" range, and that BCHE activity was not significantly correlated with age, race, body weight, cigarette smoking, or cocaine use history. There was a trend towards higher BCHE activity in subjects with a history of past alcohol abuse/dependence or with mildly elevated serum levels of liver transaminases.